Reduction In Systolic Blood Pressure Research Articles

Abstract 4131381: Comparison of Dietary Macronutrient Interventions for Weight and Cardiovascular Risk Factor Reduction: A Systematic Review and Network Meta-analysis of Randomized Controlled Trial

Background: Dietary interventions play a crucial role in weight management and reducing cardiovascular risk factors. Our study aims to compare the effectiveness of four dietary macronutrient interventions on weight loss and cardiovascular (CV) risk factor reduction through a systematic review and network meta-analysis. Methods: We conducted a comprehensive literature search on PubMed, Scopus, Embase, and Cochrane Library up till May 2024 to identify randomized controlled trials (RCTs) comparing four macronutrient dietary interventions including Mediterranean Diet (MD), Keto, Dietary Approaches to Stop Hypertension (DASH), and Intermittent Fasting (IF) with study period ≥ 6 months or 24 weeks. The primary outcomes of interest were weight loss, systolic blood pressure (SBP), Diastolic blood pressure (DBP), Body Mass Index (BMI), High density lipoprotein (HDL), Low density Lipoprotein (LDL), cholesterol levels and C-reactive protein (CRP) levels. Outcomes were reported as standard mean difference (SMD). Results: Our analysis identified 50 studies enrolling 5368 patients (MD=3554; DASH=838; Keto=206; IF=770). Regarding BP outcome, MD and DASH had significant reduction in SBP and DBP respectively (MD [SBP]: -0.76 mmHg vs DASH [DBP]: -1.92 mmHg) respectively. In contrast, IF showed a significant rise in SBP (0.87). MD participants also had significant weight loss (-1.06 kg) and a moderate decrease in BMI (-0.79) when compared with other diets. Furthermore, IF, keto, and MD showed moderate increase in HDL levels (0.61, 0.77 and 0.33) respectively. In contrast, DASH resulted in a moderate decline in HDL levels (-0.92). IF and MD resulted in modest decline in LDL levels (-0.45 and -0.42) respectively. In contrast, Keto demonstrated non-significant rise in LDL (0.35). DASH showed a significant decrease in triglycerides (-3.02). Lastly, MD demonstrated a significant reduction in CRP (-0.89). Conclusions: MD and DASH were superior to other dietary interventions in terms of weight loss and CV risk factors. Further research is required to tailor specific types of dietary interventions and assess their long-term efficacy on weight loss and CV risk reduction.

Abstract 4137479: Integrating Ambulatory Care Pharmacists into Value-Based Primary Care: A Scalable Model for Addressing Cardiometabolic Disease

Background: Chronic disease is common, costly, and complicated. In the shift to value-based payment models, interventions to engage patients and improve disease control are necessary to reduce morbidity, mortality, and cost. The use of ambulatory pharmacists has demonstrated improved management of chronic diseases. Traditionally, ambulatory pharmacists are employed by healthcare systems. In this study, we test if integrating ambulatory pharmacists hired, trained, and managed by a retail pharmacy into value-based primary care (VBPC) clinics improves care. Hypothesis: Integrating a Walgreens pharmacist empowered by collaborative drug therapy management agreements (CDTM) into Village Medical (VMD) clinics will improve indicators of chronic disease control. Aims: Improve hemoglobin A1c (HbA1c) in patients with type 2 diabetes (T2D) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in patients with hypertension (HTN). Methods: An ambulatory pharmacist was embedded into VMD clinics in Phoenix, Arizona under the supervision of VMD primary care providers via a CDTM. The pharmacist provided education, coaching, and medication management by prescribing and titrating therapies for treating T2D and HTN - enabled by access to pharmacy dispensing data. β was generated from difference-in-differences (DID) analyses with propensity score matched controls. Results: 125 patients had T2D, and 43 patients had HTN in the intervention group with 250 and 86 in the matched control group, respectively. The mean age was 65 years, 54% were female, 2% non-English speaking, and 29% racial/ethnic minorities. The average baseline HbA1c was 9% in the intervention group and 10% in the matched cohort. The average baseline SBP was 146 mmHg in the intervention group and 142 mmHg in the matched cohort. The β in the T2D group was -1.61% (p<0.001) while the β in the HTN group was -10.2 mmHg (p<0.01) for SBP and -2.0 mmHg (p=0.42) for DBP. Conclusion: We saw significant reductions in SBP and HbA1c in the pharmacist-managed group compared with matched controls. These results demonstrate that pharmacist integration into VBPC clinics may improve measures of chronic disease known to be associated with morbidity and mortality.

Abstract 4116298: Once Weekly Utreglutide (GL0034), a Glucagon-like Peptide-1 Receptor Agonist, at 4 × 450 µg Doses Reduces Blood Pressure, Lipids, and Body Weight in Post-menopausal Females: A Phase I Study

Background: Utreglutide (GL0034), a novel, once weekly glucagon-like peptide-1 receptor agonist (GLP-1RA), previously demonstrated significant reductions in body weight (BW) after a single dose ascending study in individuals with obesity . BW reductions after pharmacological treatment of obesity with GLP-1RA is associated with blood pressure (BP) lowering effects. Aim: This phase I study assessed the safety, tolerability, and cardio-metabolic effects of utreglutide after multiple ascending doses in post-menopausal female volunteers with overweight and obesity. Methods: In this randomized, double-blind, placebo-controlled study 12 post-menopausal female volunteers with overweight/obesity, aged 18 to 65 years old with a body mass index (BMI) ≥26 kg/m 2 were randomized (9:3) to subcutaneous utreglutide fixed doses (4 × 450 µg); or placebo once weekly for four weeks. Safety, tolerability, and key cardio-metabolic parameters were assessed. Biomarker measurements included oral glucose tolerance test (OGTT) insulin and glucose area under the curve (AUC), systolic- and diastolic BP, lipid profile (triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL), creatinine, potassium, BW and leptin. Results: Utreglutide was generally well tolerated and related adverse effects were mainly gastrointestinal with dose-dependent nausea, vomiting and decreased appetite. Reductions in OGTT AUCs of insulin ( p <0.05) and glucose ( p <0.01) were noted on Day 23 after four weeks treatment with Utreglutide. This was accompanied by a decrease ( p <0.001) in mean systolic and diastolic BP on Day 23 from baseline (BL). On Day 23, significant reductions in TC ( p <0.01), LDL ( p <0.05) and non-HDL ( p <0.05) were observed. BW reduction versus BL ( p <0.001) was 2.0 kg and 1.8 kg respectively on Day 29 and End of Study (EoS). Leptin levels significantly reduced from BL on Day 23 ( p< 0.01) and EoS ( p <0.001). No significant changes were observed for TG, creatinine and potassium (Table). Conclusions: Once weekly utreglutide dosing for four weeks at a dose of 450 µg in post-menopausal females with overweight and obesity, demonstrated clinically relevant reductions of systolic and diastolic BP. This was associated with improved performance of OGTT AUC of insulin and glucose, lipids, BW and leptin with an overall good tolerability and with potential to demonstrate cardio-metabolic benefits.

Abstract 4137891: Treated HIV infection is not associated with carotid vascular inflammation or plaque progression as assessed by dynamic contrast magnetic resonance imaging

Background: Inflammation and immune dysregulation are thought to drive residual cardiovascular disease risk among persons living with HIV (PLWH) despite effective viral suppression with antiretroviral therapy (ART). Question: We investigated differences in carotid vascular inflammation and atherosclerosis in a longitudinal cohort of virally suppressed PLWH (n = 50; on stable ART with CD4 >250 cells/mm 3 , viral load <200 copies/mL for >6 months) and HIV-uninfected controls (n = 51) matched for age, sex, hypertension, diabetes, smoking, hyperlipidemia, and family history of premature coronary artery disease. Methods&Results: Participants were > 40 years old at enrollment, 8% female, and had a high prevalence of cardiovascular risk factors ( Table 1 ). Measures of carotid inflammation and capillary permeability ( K trans ), neovascularization ( V p ), and wall thickness were assessed at baseline, 1 year, and change over 1 year by dynamic contrast-enhanced magnetic resonance imaging. Both PLWH and controls demonstrated a reduction in systolic and diastolic blood pressures and total cholesterol over 1 year; however, the difference was not significant by HIV status. PLWH had a significant reduction in triglycerides compared with controls (-48.8 mg/dL vs 12.8 mg/dL; p = 0.026). HIV was not associated with baseline, follow-up, or change in markers of systemic inflammation assessed by plasma cytokines (C-reactive protein, interleukin-6, interleukin-1ß), nor vascular inflammation or plaque as assessed by K trans , V p , carotid wall thickness, or percent wall volume ( Tables 2 & 3 ). Conclusions: In contrast to other studies of chronically treated and virally suppressed PLWH, HIV infection was not associated with carotid inflammation or plaque.

Assessing the impact of telemedicine interventions on systolic and diastolic blood pressure reduction: A systematic review and meta-analysis.

Hypertension, characterized by high blood pressure, poses a significant risk for cardiovascular diseases, stroke, and heart attack. Managing it is particularly challenging in areas with limited healthcare access and for patients who cannot attend regular in-person visits. Telemedicine interventions offer a promising solution by improving patient adherence and facilitating timely treatment adjustments. This study aims to systematically evaluate the impact of these telemedicine interventions on reducing systolic and diastolic blood pressure. A comprehensive search of PubMed, Scopus, and Web of Science was conducted to identify relevant studies. Two independent reviewers screened and selected eligible articles, extracting key data using a standardized form. The quality of the included studies was assessed with the Mixed Methods Appraisal Tool (MMAT). A random effects model was used to combine the results, with treatment effects measured using standardized mean differences (Hedges's g). Consistency of findings was evaluated through statistical tests, including the Q test and I² statistic, to assess heterogeneity. Data analysis was conducted using Stata statistical software version 17.0. Of the 2700 articles retrieved, 35 studies were selected for inclusion in the analysis. Using a random-effects model, the overall effect size was Hedges's g = -0.22 (95% CI: -0.30 to -0.15; p-value < 0.001), indicating a small but meaningful reduction in blood pressure (systolic and diastolic). Telemedicine interventions had a greater impact on systolic blood pressure (Hedges's g = -0.27, 95% CI: -0.39 to -0.15; p-value < 0.001) compared to diastolic blood pressure (Hedges's g = -0.17, 95% CI: -0.26 to -0.07; p-value < 0.001), though both reductions were clinically relevant. This study demonstrates that telemedicine interventions significantly reduce both systolic and diastolic blood pressure, with a more pronounced effect on systolic pressure. The overall effect size indicates a small but meaningful improvement in hypertension management. These findings highlight the potential of telemedicine as an effective strategy for enhancing patient outcomes in hypertension care.

Effect of Alternate Nostril Breathing Exercise on Cardiorespiratory Functions in Hypertensive Adults: A Systematic Review

Background: Cardiovascular diseases (CVDs), primarily driven by hypertension (HTN), are a leading global health concern. While medication is commonly used to manage HTN, non-pharmacological approaches like ANB are gaining interest. ANB is a yogic breathing technique believed to modulate the autonomic nervous system, influencing heart rate and blood pressure. Methods: A systematic review adhering to PRISMA guidelines assessed studies published between 2015 and 2022 that investigated the effects of ANB on blood pressure in human subjects. Results: Six studies were included, with findings suggesting a potential benefit of ANB for reducing blood pressure. All studies, except one, reported significant reductions in systolic and/or diastolic blood pressure after ANB practice. Intervention duration varied across studies, ranging from single sessions to six weeks of daily practice. Some studies also observed a decrease in heart rate and improved vascular function following ANB. However, limitations exist: unclear control groups in some studies and varying intervention protocols. Discussion: Despite promising preliminary evidence, further well-designed, randomized controlled trials with larger sample sizes and standardized protocols are needed. Future research should compare ANB with sham interventions or standard medical management, and explore the underlying mechanisms of how ANB might influence blood pressure. Conclusion: While the current evidence requires further confirmation, ANB appears to be a safe and potentially beneficial non-pharmacological intervention for managing blood pressure, potentially as an adjunct to medication. Healthcare professionals may consider suggesting ANB to hypertensive patients, alongside lifestyle modifications and medication, but emphasize the importance of consulting a healthcare provider before starting any new practice.

Effect of FTO Gene polymorphism on anthropometric, hemodynamic, and autonomic variables in adolescents

Objective: The study aimed to analyze the influence of physical activity levels and the rs9939609 polymorphism (FTO gene) on anthropometric, hemodynamic, and cardiac autonomic variables in public school students. Methods: A total of 288 students (aged 11 to 18, both sexes) from public schools in São Luís, Maranhão, were divided into four groups: sedentary AA+AT (AA+AT sed), active AA+AT (AA+AT activ), sedentary TT (TT sed), and active TT (TT activ). Evaluations included the International Physical Activity Questionnaire, weight, height, body mass index (BMI), buccal cells collection for DNA extraction, systolic (SBP) and diastolic (DBP) blood pressure measurements, and heart rate variability (HRV) analysis. A chi-square test for allelic associations was applied a 5% significance level. Results: No significant differences were observed in DBP or heart rate (HR). The active groups (AA+AT activ and TT activ) exhibited reductions in weight and METs/min/week compared to their respective sedentary groups (P&lt;0.05). The TT activ group also demonstrated reductions in SBP and BMI compared to the TT sed group (P&lt;0.05). The TT activ group had higher HRV in the RR time domain (ms) compared to the TT sed group (P&lt;0.05), though no significant differences were found in other HRV variables. Conclusions: The FTO gene polymorphism influences cardiac autonomic modulation, while physical activity levels affect anthropometric variables.

Differences in the effects of exercise on blood pressure depending on the physical condition of the subject and the type of exercise: a systematic review and meta-analysis.

Although hypertension is a major cause of cardiovascular disease, the control of blood pressure (BP) is insufficient worldwide. Exercise is an effective treatment for reducing BP, but the differences in the blood pressure lowering effects of exercise according to the underlying pathophysiological condition, the type of exercise, and the geographic region are not fully understood. An umbrella review with a meta-analysis of 435 randomized controlled trials that investigated the BP-lowering effects of exercise was performed using Ovid MEDLINE and the Cochrane Library, covering the period from inception to August 1, 2023. A random effects model meta-analysis was performed to estimate the effect size across multiple studies. Exercise significantly reduced systolic BP in healthy subjects (-3.51 mmHg, 95% confidence interval: -3.90, -3.11; p < 0.001) and in those with lifestyle-related diseases including hypertension (-5.48 mmHg, -6.51, -4.45; p < 0.001), but not in those with cardiovascular diseases (-1.16 mmHg, -4.08, 1.76; p = 0.44). According to the type of exercise, all types significantly reduced systolic BP in healthy subjects and in those with lifestyle-related diseases, but not in those with cardiovascular diseases. According to the region, in Oceania, there were no reductions in systolic BP. In Asia, systolic BP was reduced in patients with cardiovascular diseases. In conclusion, any type of exercise reduced BP in healthy subjects and in those with lifestyle-related diseases, but not in those with cardiovascular diseases, and the region affected the effect of exercise. When using exercise to reduce hypertension, it is important to consider the patient's pathophysiological condition and the region.

Isometric handgrip versus aerobic exercise: a randomized trial evaluating central and ambulatory blood pressure outcomes in older hypertensive participants.

It remains unclear whether the hemodynamic effects of isometric handgrip exercise (IHG) are comparable to those of aerobic exercise (AE). This study investigated the efficacy of IHG in reducing central and ambulatory blood pressure in older hypertensive participants and compared its effects with AE. In a three-arm randomized controlled trial, 54 older hypertensive participants (age range: ≥60; mean age: 69 years) underwent 12 weeks of either IHG training (n = 17), AE training (n = 19), or were part of a no-exercise control group (n = 18). IHG participants engaged in bilateral handgrips using a digital device, four times for 2 min each at 30% of maximal voluntary contraction. AE participants undertook brisk walking and cycling exercises at moderate intensity for 30 min, thrice weekly. Baseline and postintervention measurements included resting office, central, and 24-h ambulatory blood pressures. Both IHG and AE interventions led to significant reductions in office and ambulatory systolic blood pressure compared to control group (P < 0.05 for both), with no marked difference in the magnitude of systolic blood pressure reductions between the two groups. Notably, the IHG group exhibited greater reductions in office, central, and ambulatory diastolic blood pressure compared to the AE group and control group. While both IHG and AE effectively lowered ambulatory systolic blood pressure, IHG demonstrated superior efficacy in reducing central and ambulatory diastolic blood pressure. Consequently, IHG training presents a promising alternative antihypertensive therapy for hypertensive participants over the age of 60.

Effect of nebivolol monotherapy or combination therapy on blood pressure levels in patients with hypertension: an updated systematic review and multilevel meta-analysis of 91 randomized controlled trials.

To systematically appraise and summarize the available evidence from published randomized controlled trials considering the effect of nebivolol on blood pressure in patients with hypertension. Literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until December 15, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis. In total, 7,737 participants with hypertension, who were treated with nebivolol, were analyzed across 91 RCTs. Nebivolol was associated with significantly greater reduction in office systolic and diastolic BP compared to placebo (MD = - 6.01 mmHg; 95% CI = [- 7.46, - 4.55] and MD = - 5.01 mmHg; 95% CI = [- 5.91, - 4.11], respectively). Moreover, resulted a similar reduction in systolic BP (MD = - 0.22 mmHg; 95% CI = [- 0.91, 0.46]) and a significantly greater reduction in diastolic BP compared to the active comparator (MD = - 0.71 mmHg; 95% CI = [- 1.27, - 0.16]). When considering the effect of nebivolol on 24-hour ambulatory BP, notable reductions were observed compared to placebo. In contrast, compared to the active comparators, there was no significant difference in systolic BP reduction, but a significant reduction in diastolic BP favoring nebivolol. Based on moderator analyses, the impact of nebivolol on the pooled estimates remained independent of the dose of nebivolol, age, male sex, trial duration, body mass index (BMI), baseline diabetes, heart failure, and baseline systolic and diastolic BP. Nebivolol, compared to placebo, showed a significant BP reduction and was non-inferior to other active comparators in terms of BP reduction.

Safety, tolerability and blood pressure lowering of the innovative guanylyl cyclase a-receptor activator MANP in an ethnically diverse resistant hypertension population: a phase 1B clinical trial

Abstract Background/Introduction MANP is a novel atrial natriuretic peptide (ANP) analog bioengineered as a particulate guanylyl cyclase A receptor (GC-A) activator with superior receptor binding, resistance to neprilysin degradation, natriuretic, aldosterone suppressing and blood pressure (BP) lowering properties than native ANP. MANP is now under clinical development for resistant hypertension (RH). The rationale for its design was the fundamental role of the ANP/GC-A system in BP homeostasis through which GC-A activation with MANP leads to BP reduction through renal, vascular, and hormonal mechanisms mediated by the second messenger cGMP. Purpose We investigated the safety, tolerability, cGMP activation and BP reductions of MANP compared to placebo in subjects with RH. Methods We performed a double-blind, placebo controlled randomized trial in 36 RH patients comprised of approximately 50% non-African Americans (NAA) and 50% AA. MANP was administered in 6 cohorts receiving ascending subcutaneous (SQ) doses of MANP once daily from 3 ug/kg to a maximal dose of 7 ug/kg or placebo for 5 days and then followed for 21 days after dosing. Endpoints included safety, cGMP activation and changes in systolic BP (SBP), aldosterone (Aldo) levels and glomerular filtration rate (GFR). Results MANP was safe and well tolerated. One patient in the 7 ug/kg cohort was discontinued due to symptomatic hypotension. Compared to baseline, plasma cGMP increased in all MANP groups on Day 1 and Day 5 with no change in the placebo group. The maximal SBP reduction in the MANP group on Days 1 (D1) and 5 (D5) was -17.5 (D1) and -16 mmHg (D5) with 3 ug/kg (lowest dose) and -39.5 (D1) and -36.3 mmHg (D5) with 7 ug/kg (highest dose); Changes in the Placebo group were -6.3 (D1) and -16.7 mmHg (D5). Notably, the SBP reductions in AA were greater than NAA in the 4 and 7 ug/kg cohorts. After the 1-hour timepoint on both the first and fifth days, Aldo and percentage of Aldo reduction generally remained suppressed compared to baseline. Twenty-one days after MANP dosing, SBP remained lower in three groups receiving SQ MANP (4, 4.5 and 7 ug/kg) compared to placebo in association with a preservation of GFR. There were no reported drug related serious adverse events. Conclusions This clinical trial demonstrates that once a day SQ administration of MANP in RH subjects activates cGMP, without attenuation over 5 days, and reduces SBP and preserves GFR. At higher doses of MANP, SBP reductions were greater in AA compared to NAA. MANP also demonstrated Aldo inhibiting actions compared to placebo. Importantly, MANP was overall safe and well-tolerated. Our findings support the continued clinical development of MANP as a novel GC-A activating peptide for the treatment of RH.

Subgroup results from KARDIA-2: impact of demographic and baseline disease characteristics on zilebesiran response in patients with hypertension uncontrolled by a standard oral antihypertensive

Abstract Background Zilebesiran is an investigational RNA interference therapeutic targeting hepatic angiotensinogen synthesis. In KARDIA-1, a single subcutaneous (SC) dose of zilebesiran monotherapy significantly reduced 24-hr mean ambulatory and office systolic blood pressure (SBP) from baseline to Months 3 and 6 versus placebo. The Phase 2 KARDIA-2 study assessed efficacy and safety of zilebesiran with a standard oral antihypertensive in patients with uncontrolled hypertension. Purpose Uncontrolled hypertension is a leading cause of cardiovascular morbidity and mortality, and medication non-adherence affects blood pressure control. Developing effective, long-lasting treatments is crucial for patients with hypertension uncontrolled by standard therapy. Methods KARDIA-2 enrolled adults with mild-to-moderate hypertension who were untreated or receiving stable therapy with ≤2 antihypertensives. Patients discontinued prior antihypertensive medication and were randomized 10:7:4 to open-label, once-daily oral treatment with 40 mg olmesartan, 5 mg amlodipine, or 2.5 mg indapamide. After ≥4 weeks on protocol-specified medication, patients with a 24-hr mean ambulatory SBP of 130–160 mmHg were randomized 1:1 in a double-blind manner to a single SC dose of zilebesiran 600 mg or placebo as add-on therapy. The primary endpoint was change from baseline to Month 3 in 24-hr mean ambulatory SBP versus placebo for each group. Efficacy and safety were also assessed in pre-specified subgroups: age (&amp;lt;65; ≥65 years), sex, race (Black; other), baseline 24-hr mean ambulatory SBP (&amp;lt;145; ≥145 mmHg), and baseline estimated glomerular filtration rate (≥60; &amp;lt;60 mL/min/1.73m2). Results The primary analysis included 667 patients (median age [range] 59 [27–75] years; 57% male, 28% Black). At Month 3, least-squares mean differences (LSMD) (95% confidence interval [CI]) between zilebesiran and placebo for the olmesartan, amlodipine, and indapamide groups were −4.0 (−7.6, −0.3), −9.7 (−12.9, −6.6), and −12.1 (−16.5, −7.6) mmHg, respectively, for 24-hr mean ambulatory SBP (all p&amp;lt;0.05). LSMD (95% CI) in office SBP for the same groups were −7.0 (−10.4, −3.6), −10.2 (−13.5, −6.9), and −18.5 (−22.8, −14.2) mmHg, respectively, (all p&amp;lt;0.001). SBP reductions were consistent across subgroups, except for a trend towards an attenuated response observed in Black patients (Figs 1, 2). More patients receiving zilebesiran (49–58%) than placebo (39–48%) experienced ≥1 adverse event through Month 6, with low rates of hyperkalaemia, hypotension, or acute kidney injury reported across all groups. Conclusion In KARDIA-2, a single dose of zilebesiran significantly reduced SBP versus placebo at Month 3 on top of a standard oral antihypertensive, with encouraging safety data. SBP reduction was consistent across most subgroups. Treatment with zilebesiran combined with standard antihypertensives may be effective for a broad population of patients with hypertension uncontrolled on monotherapy.

Trends in hypertension prevalence and control in England over the last 3 decades: Health Survey of England 1994-2019

Abstract Globally, raised blood pressure (BP) contributes to more than 10.8 million avoidable deaths from cardiovascular (CV) and renal disease. Understanding national BP control trends amongst hypertensive patients will help inform the effectiveness and gaps in existing pathways and policies. We used data from 13 nationally representative health surveys in England between 1994-2019 to compare nationwide trends in BP control and hypertension awareness over 25 years. We used ‘period’ definitions to define hypertension and BP control (i.e. using existing guidance at the time of the survey) to account for changes in BP targets and definitions. Analyses were also conducted using ‘current definitions’ (i.e. definition of hypertension and BP control targets as per NICE 2023), applied across the entire duration. Sample weights, accounting for oversampling and survey nonresponse, and other relevant transformations were applied. Python and STATA 18 were used to conduct analyses and Join Point regression software was used to compare trends. In England, between 1994-2019, the prevalence of hypertension initially increased sharply by 8% from 23.3% when the BP cut off was lowered in 1999. Thereafter for the next 12 years it remained static at 32-34%, and since 2011 has plateaued at 31-32%, showing only marginal improvement of 1.5% over this 25-year period (Figure 1). This is consistent with population-wide mean systolic (S) and diastolic (D) BPs, and amongst those with and without hypertension. Population-wide there was a reduction in SBP (8.5mmHg) and DBP (3.8mmHg) over the period. There was significantly greater reduction in SBP (11.9 vs 9.5mmHg) and DBP (4.1 vs 2.5mmHg) amongst those with diagnosed hypertension as compared to those without. Using the current target of below 140/90mmHg when evaluating BP control over this period suggests that we have improved. However, when we use ‘period definitions’ of BP targets at that time, it seems that over last 25 years there has been ‘no change’ in the proportion of diagnosed hypertensives with uncontrolled BPs (Figure 2). Additionally, although appearing to increase over the period, there has been no significant change in proportions of those with hypertension who are unaware of this condition since BP cut-offs were lowered in 1999. These findings indicate that in England, over last 25 years, whilst there have been some improvements in population wide mean SBP and DBP with slight reduction in hypertension prevalence, the proportions of those with known hypertension with uncontrolled BPs have remained static. This is despite improvement in medications and practice. Furthermore, there has been little progress in detection of those hypertensive patients who are unaware about and untreated for their condition. Clearly, these call in question the effectiveness of the current policies and clinical practice pathways and provide huge opportunity to improve population wide CV riskSytolic and Diastolic BP trendsTrends in the prevalence of BP control

Blood pressure lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of 500 randomised, double-blind placebo-controlled trials

Abstract Background Each 1 mmHg reduction in systolic blood pressure (SBP) reduces the risk of major cardiovascular disease events by about 2%. However, there are currently no tools to provide randomised trial-derived estimates of blood pressure (BP)-lowering efficacy of different antihypertensive regimens despite the vast number of possible drug-dose permutations. There has also been no attempt to classify efficacy of treatment regimens into low, moderate, and high intensity. Purpose We aimed to quantify the BP-lowering efficacy of the five major classes of antihypertensive drugs and their combinations. Methods We conducted a systematic review and meta-analysis of randomised double-blind placebo-controlled trials. CENTRAL, MEDLINE and Epistimonikos were searched from inception until December 2022 to identify trials, that compared angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, calcium channel blockers, and diuretics versus placebo, for 4-26 weeks. Primary outcomes were reduction in SBP and diastolic blood pressure (DBP). Doses were classified into standard dose based on the World Health Organisation Defined Daily Dose. BP-lowering efficacy was estimated for each drug and dose using fixed-effects meta-analyses and meta-regressions, standardised to baseline SBP 154 mmHg. Treatment regimens were categorised into low, moderate, and high intensity according to estimated SBP-lowering efficacy of &amp;lt;10, 10-19 and ≥20 mmHg, respectively. Results A total of 500 trials (106,358 participants, 44% female) were included, which included 66 single antihypertensive drugs (monotherapy) and 89 two drug (dual) combinations. The mean baseline BP was 154/100 mmHg and mean follow-up was 8.6 weeks. Monotherapy at one standard dose reduced SBP by 8.5 (95% CI, 8.2-8.9) mmHg, with an additional 1.2 (1.0-1.5) mmHg reduction for each 10 mmHg higher pre-treatment SBP, and an additional 1.5 (1.2-1.8) mmHg reduction with each doubling in dose. There was significant heterogeneity between monotherapies, and 72% were classified as low intensity efficacy. Dual combinations at one standard doses of both the drugs reduced SBP by 15.2 (13.4-17.1) mmHg, and an additional 2.6 (1.4-3.8) mmHg reduction with doubling the doses of both the drugs. There was considerable heterogeneity between dual combinations and 59% were classified as moderate, and 11% as high intensity efficacy. The BP lowering efficacy of adding additional drug classes was confirmed to be additive after accounting for pre-treatment SBP. Triple combinations were classified as high intensity efficacy based on meta-regression analyses. Conclusions There is significant variability in the efficacy of different BP-lowering regimens. The present analyses, available in an online tool, can estimate the BP lowering efficacy for any combination of drug(s) and dose(s), and can classify treatment regimens into low, moderate or high intensity.

Assessing the efficacy of renal denervation in patients with resistant arterial hypertension: a systematic review and meta-analysis

Abstract Background/Introduction Renal denervation (RDN) is an innovative procedure designed to regulate the renal sympathetic nervous system for the control of arterial hypertension (HTN). RDN emerges as an alternative for patients with resistant arterial hypertension. Despite this, the clinical efficacy of RDN is still not fully understood. Purpose Therefore, we aimed to compare the use of renal denervation versus sham procedure or pharmacological treatment in patients with resistant HTN. Methods We performed a systematic search of PubMed, Embase, Cochrane databases for randomized controlled trials (RCTs) comparing the use of renal denervation procedures and sham procedure or pharmacological treatment in patients with resistant HTN. Statistical analyses were performed using R Studio 4.3.2. Heterogeneity was examined with the Cochran Q test I² statistics. Mean difference (MD) with 95% CI were pooled across trials. P values of &amp;lt; 0.05 were considered statistically significant. The primary continuous outcomes of interest were change from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP) and serum creatinine. Results Twenty-one RCTs reporting data on 3345 patients were included in this meta-analysis. Among them, 2004 (59,91%) received renal denervation and 1341 (40,09%) received pharmacological treament or sham procedure. Follow-up ranged from 2 to 48 months. The mean age of patients between studies ranged from 50.7 to 65 years. Compared to control group, RDN significantly reduced Systolic Blood Pressure (SBP) (MD -3.53 mmHg; 95% CI -5.94 to -1.12; I2 = 74%) and Diastolic Blood Pressure (DBP) (MD -1.48 mmHg; 95% CI -2.56 to -0.40; I2 = 51%). Regarding serum creatinine (MD -2.51; 95% CI -7.90 to 2.87; I2 = 40%) there was no significant difference between RDN and control groups. Conclusion In this meta-analysis of RCTs of patients with resistant HTN, RDN was associated with a reduction in SBP and DBP compared to sham procedure or pharmacological treatment.

Effect of incremental exercise training interventions in a Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Exercise-based cardiac rehabilitation is recommended after myocardial infarction (MI) to improve prognosis, quality of life and control of cardiovascular risk factors. However, the specific impact of different exercise training interventions remains incompletely understood. Purpose To study the health outcomes of three incremental exercise training interventions during a Cardiac Rehabilitation Program (CRP) following MI. Methods We implemented a post-MI Phase 2 CRP in 2022. After initial exercise testing, a 3-month, individualized aerobic and strength ambulatory training program was provided by Cardiologists and Physical Medicine and Rehabilitation physicians (Group 1, n=58). Additionally, a subset of patients received one session of supervised teaching of aerobic and strength training by physiotherapists (Group 2, n=19), and another subset received 8-20 sessions of in-hospital supervised training (Group 3, n=13). Exercise testing was repeated at the end of Phase 2 and peak oxygen consumption (peak VO2) was measured. We analysed quality of life (SF-36), depression (PHQ2), anxiety (GAD2), adherence to Mediterranean diet (PREDIMED) and pharmacological treatment (Morisky-Green), and weekly physical activity (IPAQ). Health outcomes were compared at the beginning and after Phase 2 CRP. Results The cohort comprised 90 patients who completed Phase 2 CRP (mean age 61.2±10.8 years, 84.4% male and 47.8% smokers). Reductions in systolic blood pressure (-10.3±13.8mmHg), LDL cholesterol (-60.7±35.4mg/dL), weight (-2.8±6.6kg, -3±7.8%) and body mass index (-1±2.2) were attained (p&amp;lt;0.05). Smoking abstinence was accomplished in 88.4% of smokers and most patients achieved an LDL&amp;lt;55mg/dL (81.1%). Improvements in quality of life (SF-36 +10.4±19.4 points, p&amp;lt;0.001) and anxiety and depression symptoms (PHQ2 -0.5±1.6 points and GAD2 -0.6±1.6 points, p&amp;lt;0.01) were noted. An increase in peak VO2 (+5.12±5.44ml/kg/min, +23.5±27.4% from baseline, p&amp;lt;0.001) and predicted functional capacity (+13.4±23.8%, p&amp;lt;0.001) was achieved. Patients increased their reported weekly physical activity by 2520.3±2935.4 METS/week (+132% from baseline, p&amp;lt;0.001) and most of them were adherent to Mediterranean diet (91.1%) and pharmacological treatment (95.6%). Patients achieved similar health outcomes regardless of their exercise training group, except for patients in Group 3, who experienced a more pronounced improvement in peak VO2 (+8.1±6.4ml/kg/min, +37.8±34.7% from baseline; p&amp;lt;0.05) and a trend towards higher increase in predicted functional capacity (+21.7±19.2%, p&amp;lt;0.25) and greater weight loss (-5.5±9.4kg, -5.9±9.6%; p&amp;lt;0.2). Conclusions Supervised in-hospital training during a Phase 2 CRP provides superior physical fitness improvements and more pronounced weight loss in MI patients. However, a Phase 2 CRP based on ambulatory training provides similar benefits regarding other health outcomes, such as control of cardiovascular risk factors and quality of life amelioration.Exercise training interventions in a CRP

Dapagliflozin enhances arterial and venous compliance during exercise in heart failure with preserved ejection fraction

Abstract Background Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. Purpose This study tested the hypothesis that SGLT2i dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. Methods In this secondary analysis from the RCT trial, patients with HFpEF underwent invasive hemodynamic exercise testing at baseline and following treatment for 24 weeks with dapagliflozin or placebo. Patients were required to display pulmonary capillary wedge pressure (PCWP) ≥25 mmHg during exercise at the time of baseline evaluation. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated (eSBV) from hemodynamic indices fit to a comprehensive cardiovascular model. Results A total of 37 patients completed the study and were included in this analysis (21 dapagliflozin and 16 placebo). Patients were predominantly women (24/37, 65%) and older (mean age 67 years). There was no statistically significant effect of dapagliflozin on resting BP, but dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mmHg, 95% CI: -33.9 to -3.7, P=0.016) (Figure 1A). Dapagliflozin improved exertional total arterial compliance (TAC) index (ETD, 0.06 mL/mmHg/m2, 95% CI: 0.003 to 0.11, P=0.039) (Figure 1B) and aortic root characteristic impedance (ETD, -2.6 mmHg/ml*sec, 95% CI: -5.1 to -0.03, P=0.048) during peak exercise, with no significant effect on systemic vascular resistance. Dapagliflozin reduced eSBV at rest and during peak exercise (ETD, -292 mmHg, 95% CI: -530 to -53, P=0.018) (Figure 1C), and improved venous capacitance evidenced by a decline in ratio of eSBV to total blood volume (ETD, -7.3%, 95% CI -13.3 to -1.3, P=0.020). Each of these effects of dapagliflozin during peak exercise were also observed during matched 20W exercise intensity. Improvements in TAC index and eSBV were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in eSBV during exercise (r=0.40, P=0.019) (Figure 2A). Decreases in BP were correlated with reduction in PCWP during exercise (r=0.56, P&amp;lt;0.001) (Figure 2B). Conclusion In patients with HFpEF, treatment with dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with SGLT2i in HFpEF.

Do more with less? Impact of personalized very low doses of amlodipine in the PERSONAL-CovidBP trial

Abstract Introduction The Personal-CovidBP study1 tested remote patient use of a drug-device combination of a smartphone application (App) to record blood pressure (BP), novel personalized milligram-by-milligram drug (amlodipine) dose, and relevant side effects daily during the COVID-19 pandemic. Purpose In supplementary data analyses, we examined the effect of using small doses (1 mg) and small increments (1-2 mg) of amlodipine on the BP response and side effects. Methods In this community-based trial with remote monitoring and remote medical management from the investigational site, hypertensive participants aged 18 years + with poor BP control (prior 7 day mean of 135 mmHg systolic BP or above and/or 85 mmHg diastolic BP and above) were enrolled to intervention with open label dose titration over 14 weeks, allowing personalized dosing of liquid amlodipine (1–2 mg steps from 1–10 mg daily). Results 205 patients were enrolled into the intervention group between October 2020 and July 2021. Average BP in intervention fell from 141/87 to 131/81 (difference −10/6 p &amp;lt; 0.001). Even low doses or small increments: 1 or 2 mg amlodipine or 5 mg to 6 mg, produced meaningful BP responses. Here we report that the addition of amlodipine during the study reduced blood pressure regardless of being amlodipine naive at baseline (n=141), or receiving amlodipine 2.5mg or 5mg at baseline (n=62). The response slopes were comparable, and mean reductions in SBP were consistent across groups: -11.7 (95% CI: -12.9 to -10.6); -9.4 (-11.1 to -7.7); respectively (Figure 1). For the amlodipine naive, the majority (76%) achieved BP control at low doses (&amp;lt;1 to 3mg) with occurrence of side effects increasing with dose (Figure 2). Conclusions Our real-world remote care study demonstrated that very low doses of amlodipine as little as 1 mg were effective and for 1mg-3mg gained BP control in the majority and were associated with fewer side effects which is consistent with previous meta-analyses.2 Personalized treatment titration was effective even at very low doses and also regardless of whether amlodipine naive or not at baseline.Changes in SBP- baseline amlodipine useAmlodipine dose at control vs oedema

Relationships among intensive blood pressure control, morning blood pressure surge and 24-hour blood pressure variability

Abstract Objectives This study aimed to investigate the relationships between cardiovascular outcomes and blood pressure (BP) reduction, 24-hour BP variability (BPV), morning BP surge (MBPS), and visit-to-visit BPV. Methods This study involved 897 participants from the Systolic Blood Pressure International Trial (SPRINT), for whom biochemical and demographic data, medication history, and various blood profile information were collected. Univariate and multivariate linear regression models were used to assess the impact of intensive BP management on 24-hour BPV and the MBPS. Results Among the 897 participants (average age 71.48 ± 9.42 years; 640 males), 453 received intensive treatment. Those in the intensive group were more likely to be on ACE inhibitors, CCBs, or diuretics. This group showed significant reductions in 24-hour systolic and diastolic BP, as well as in both short-term and long-term BPVs, such as average real variability (ARV) and MBPS. The analysis demonstrated strong associations between intensive BP management and improvements in various BPV measures, including systolic ARV, diastolic BP ARV, and cumulative BP loads. A significant correlation was also found between intensive BP lowering and the primary composite outcome of the SPRINT study. Conclusions This study highlighted the significant associations between intensive BP management and reductions in the MBPS and 24-hour BPV, which affect both short-term and long-term health outcomes. The primary benefits of intensive BP control appear to stem from direct BP reduction rather than changes in BPV. However, further extensive randomized controlled trials are needed to confirm these findings.

Nationwide trends in blood pressure control among those with and without diabetes in England over last 2 decades: Health Survey of England 2003-2019

Abstract Diabetes and hypertension are both risk factors for cardiovascular disease (CVD), and often co-exist. Over recent decades practice guidance and health policy efforts have been made to improve population wide blood pressure (BP) control, particularly amongst those with diabetes, to reduce CVD. However, the nationwide impact of these ongoing efforts is yet to be documented comprehensively in England. We used data from 11 serial nationally representative health surveys of England between 2003 and 2019 and compared BP control and presence of untreated hypertension amongst those with and without diabetes. These cross-sectional, randomly sampled surveys included 94,100 individuals cumulatively. We applied sample weights, accounting for oversampling and survey nonresponse, and transformations mitigating for survey equipment changes during this period. We used ‘period definitions’ to define those with diabetes and quantify BP control at the time of each coinciding survey, facilitating accurate comparison of trends over the sixteen-year period, while accounting for changes in understanding, variations in definitions, and shifts in medical practices. Python and STATA were used to conduct analyses and Join Point regression software was used to develop and compare trends. In England, from 2003-2019, the prevalence of hypertension amongst those with diabetes and without diabetes decreased from 74.4% to 66.5% and from 32.6% to 27.1% (7.9% vs. 5.5%), respectively. This corresponded to reductions in population-wide mean systolic (S) and diastolic (D) BPs: compared to those without diabetes, those with diabetes had greater reduction in both SBP (7.9mmHg vs. 4.8mmHg) and DBP (2.7mmHg vs. 1.9mmHg) (Figure1). Both groups showed similar temporal improvement in BP-control amongst those with diagnosed hypertension, with those with diabetes showing better improvement in BP control compared to those without diabetes (14% vs. 12%). There was a significant difference in proportions of those with undiagnosed (unaware) hypertension amongst those with and without diabetes (11.4% vs. 30.0% respectively) (Figure2). Notably, there was no change in proportion of those with hypertension unaware about the condition (i.e. detection rate for hypertension in either of the group did not show any improvement over time). These results suggest that we have been able to improve BP control over this period amongst those with and without diabetes, however, those without diabetes (more than 90% of population) have shown significantly poorer improvement. In addition, around one third of hypertensive patients amongst the no-diabetes group are unaware of the condition, and overall, the detection rates for hypertension in both groups have not improved in the last two decades. Lessons learnt from improving BP control amongst those with diabetes should be applied across the entire population, and newer strategies need to develop to improve detection of those with hypertension and are unaware.